Table 1.

Major findings reported in vascularized liver-on-a-chips.

Disease Model	Cell Lines	Major Findings	Reference
Inflammation Fibrosis/Cirrhosis HCC	HepG2 C3Asub28 LX-2 THP-1 TIME	● Cirrhosis and inflammation increased vascular damage, and permeability due to upregulated inflammatory cytokines. ● High CYP3A4 expressing HCC cells increased vascular damage and permeability.	Özkan et al. [9]
Inflammation	Primary hepatocytes LX-2 THP-1 LSECs	● LSECs activated by LPS promoted α-SMA expression of stellate cells. ● α-SMA expression of activated stellate cells was higher in zone 3 compared to zone 1.	Li et al. [67]
Inflammation Fibrosis/Cirrhosis	Rat PMVECs HPMECs HCMECs HDMECs	● Increase in matrix stiffness upregulated production of podosomes, actin-based structures involved in cell adhesion, migration, invasion, and ECM degradation, independent of classical podosome inductors VEGF and TGF-β.	Juin et al. [101]
Inflammation Fibrosis/Cirrhosis	LSECs	● Increase in substrate stiffness upregulated the expression levels of VCAM-1 and ICAM-1 in LSECs.	Natarajan et al. [102]
ALD/NAFLD	HepG2 LX-2 EAhy926 U937	● Increase of ethanol concentration decreased VE-cadherin expression of endothelial markers, resulting in a potentially leakier vasculature. ● eNOS was downregulated when exposed to high doses of exposure to ethanol.	Deng et al. [103]
ALD/NAFLD	Rat hepatocytes HUVECs	● Co-culture of hepatocytes with HUVECs doubled chain fatty acid family members compared to a monoculture.	Takayama et al. [104]
Hepatitis B	Rat Hepatocytes BAECs	● Co-culture with endothelial cells sustained longer and consistent secretion of urea and also improved and sustained liver specific differentiation markers such as albumin, transferrin hepatocyte nuclear factor 4, and β-actin compared to hepatocytes alone.	Kang et al. [105]
Hepatitis B	Rat Hepatocytes BAECs	● HBV infected hepatocytes and BAECs showed that hepatocytes with HBV lost their native morphology within a week without the presence of BAECs.	Kang et al. [106]
Fibrosis/Cirrhosis	LSECRat KCs	● HBV passing through endothelium fenestrate and infecting the hepatocytes. ● Increase in matrix stiffness decreased LSEC proliferation and increased the size of adhesion sites, loss of fenestrae, expression of CD31, while substantially altering cell morphology.	Ford et al. [107]
Healthy Liver HCC	MDA-MB-231 THLE-3 C3Asub28 TIME	● Endothelial co-culture with HCC cells experience EPR effect unlike co-culture with healthy liver. ●70 kDa dextran (size of chemotherapy+NP) accumulated less in healthy liver than 3 kDa dextran particles (plain chemotherapy).	Özkan et al. [8]